We propose to repurify or resynthesize a selection of previously prepared prostaglandin analogs (PGD2, PGF2 alpha and PGA2 mimics) and determine their effects on in vivo platelet function, vascular smooth muscle, endothelial thromboresistance, and the modification of platelet consumption by prosthetic materials. In these tests we will be looking not only for agonist properties but also antagonist activities and enzyme (PGI2 and TXA2 synthetase) inhibitions. While these analogs are being tested, the chemical program will be centered on design and construction of test substances bearing key structural features of PGD2, TXA2, and prostacyclin (PGI2). Particular goals are chemically stable mimics of prostacyclin and thromboxane A2 (TXA2). The newly constructed analogs will be tested for cardiovascular activity, as inhibitors of PGD2, PGI2, and TXA2 action, and as potential inhibitors of the various enzymes involved in arachidonate metabolism in the cardiovascular system. The stress points of the pharmacological screen are: platelet aggregation, endothelial thromboresistance, and vascular tone maintenance. Polymer-tethered prostacyclins will be synthesized in order to assess the nature of the prostacyclin-platelet interaction, the location of the receptor, and whether binding to an outer membrane located receptor is a sufficient stimulus for platelet function inhibition.